Failure to wean patients from mechanical ventilation (MV) is a medical, economic and social problem. Approximately 40% of the time patients spend in ICU on MV is devoted to weaning. Numerous algorithms to predict weaning outcome have been published, but few studies have examined the specific treatment of weaning failure. The traditional approach to MV weaning has focused on optimizing medical care and the patient-ventilator interface, but there is growing evidence that MV use leads to inspiratory muscle weakness and this weakness is a major contributor to MV dependence. We have developed a practical rehabilitation approach to improving inspiratory muscle strength in MV dependent patients to facilitate weaning. We have assembled a team of physicians, a rehabilitation specialist, a respiratory physiologist, a communication specialist and developed a systematic rehabilitation approach to treating MV dependence due to inspiratory muscle weakness. We propose to study the effectiveness of threshold inspiratory muscle strength training (IMST) to improve weaning outcome in MV dependent patients. We will test the hypothesis that threshold IMST will increase the inspiratory pressure generating capacity of MV dependent patients, decrease the time required to wean these patients from MV and increase the proportion of patients weaned. MV dependent patients in ICUs will be divided into 2 groups: a SHAM group and an IMST group. Both groups will receive an identical MV management strategy with progressively lengthening spontaneous breathing trials as tolerated. The IMST group will receive up to 6 weeks of high intensity, low repetition training using a threshold inspiratory muscle trainer. The SHAM group will receive a training program for an equal period of time. The personnel providing the IMST and SHAM treatments and the subjects will be blinded to the treatments. Groups will be compared on the number of subjects weaned, the duration of time needed to wean following protocol completion and changes in breathing pattern. The results of this work will provide new information on an inspiratory muscle strengthening rehabilitation approach to weaning for MV dependent patients. This study will illuminate the mechanisms mediating MV dependence in these patients and lead to effective treatment strategies for patients dependent upon MV due to respiratory muscle weakness. [unreadable] [unreadable]